In FY18, we focused on iPSC gene-editing technologies and iPSC-cardiomyocyte studies: We continue to develop robust CRISPR/Cas9 technologies for iPSCs to accomplish more sophisticated genome engineering projects. Using improved single-cell sorting, serial dilution, and culture methods, we can obtain gene-edited clones in shorter time and with higher purify. We also compared several CRISPR/Cas9 delivery systems, using plasmid, RNA or RNP, by transfection or electroporation. We selected the most efficient and cost-saving method to achieve high-quality gene-editing results and meet high demand from our users. Besides achieving gene knockout at 20-80% efficiency as well as precision gene correction or mutation knockin at 0.5-5% efficiency, we are able to increase the productivity of these established gene-editing services. In FY18, we offered large gene-deletion project as a new iPSC gene-editing service. We finished 12 gene knockout projects, 4 gene correction or mutation knockin projects, 3 gene-deletion projects, and 3 AAVS1 safe harbor knockin projects within this fiscal year. The total 22 projects exceeds any previous year since we introduced iPSC gene editing service in FY15. These genetically modified iPSC lines are being used as isogenic control lines to model human hematopoietic, neurological, or metabolic diseases. We continue to provide high-quality, integration-free iPSC generation services. In FY18, we reprogrammed 105 blood samples and 85 skin fibroblast samples, nearly doubling the amount of the samples received in FY17. The 190 iPSC lines in FY18 not only was the highest number of cell lines we generated in any fiscal year since the Core was established in 2011, but also increased the total iPSC lines we generated so far to more than 630 lines. While iPSC generation service is the major contributor to our total cost recovery, gene-editing services reached 30% of total cost recovery in FY18 and is on the track to replace iPSC generation as the most popular services. Thanks to strong demand for both iPSC generation and gene-editing services, we were able to recover >30% of our total budget in FY18. Based on our chemically defined iPSC-cardiomyocyte (iPSC-CM) differentiation protocol, we studied regulation of iPSC-cardiomyocyte differentiation and used human iPSC-CM to investigate drug-associated cardiotoxicity. We found heparin can regulate Wnt signaling, and adding heparin to DMEM/F12-based chemically defined medium allows quick and efficient cardiomyocyte differentiation. We also found nonhuman primate (monkey) iPSC-cardiomyocyte differentiation is inefficient if only using chemical compound to induce Wnt. Instead, the combination of BMP4, ActA, and bFGF is needed to induce cardiac mesoderm, probably due to dynamic balance of gene expression levels in early mesoderm induction. These two studies resulted in two published papers in Stem Cell Translational Medicine and Scientific Reports in FY18. We continue to make significant contribution to nonhuman primate iPSC-cardiomyocytes transplantation project, which includes 7 NHLBI investigators and 2 extramural collaborators. We generated large quantities of CD19 labelled monkey iPSC-CMs that are being used for allogenic transplantation experiment. We are also using another non-immunogenic marker, NIS, for upcoming autologous and allogenic transplantation. We have confirmed that monkey iPSC-CMs expressing NIS in a safe-harbor locus maintain normal electrophysiological characteristics, can engraft in a mouse myocardial infarction (MI) model and be detected easily by non-invasive in vivo imaging. We have deposited our iPSC gene editing vectors in non-profit repository Addgene (https://www.addgene.org/Jizhong_Zou/ ), who has distributed our vectors for 354 times to 226 laboratories in 163 non-profit research institutes in 24 countries worldwide. In FY18, we gave lectures in a FAES course on iPSC gene editing and neural differentiation. We presented posters at NHLBI DIR Research Festivals, NHLBI cardiovascular regenerative medicine symposia, and annual ISSCR meeting. We authored and co-authored 5 papers in FY18.